U.S. Pat. No. 3,468,894 disclosed the 1-unsubstituted 3-methyl-2-(3- or 4-pyridyl)indoles as diuretic agents. 2-(2-Pyridyl)indole-3-(acetic, propionic) acids are reported e.g., in Pharm. Bull. 4, 16 (1956) and Chemical Abstracts 64, 19540d (1966) respectively. Various optionally substituted 2-(3-pyridyl)-indole-3-acetic acids have been described as chemical intermediates in Bull. Soc. Chim. France 1966, 771-2 and Bull. Soc. Chim. France 1969, 4154-9. The preparation of 1-cyanoethyl-2-(2-pyridyl)-indole is reported in Pharmazie 23 (10), 557-60 (1968).
Reported as thromboxane synthetase inhibitors are e.g., 3-(imidazol-1-yl-alkyl)indoles of U.S. Pat. No. 4,217,357 and 4,273,782 and 1-substituted imidazoles of U.S. Pat. No. 4,256,757 and British patent application No. 2,016,452A.
The present invention is concerned with N-(or 1)-substituted-2-pyridylindoles of formula I representing a novel class of pharmaceuticals. For example, the compounds of formula I are surprisingly potent and highly specific thromboxane synthetase inhibitors.
The foregoing attributes render the N-substituted-2-pyridyl indoles of this invention particularly useful when administered, alone or in combination, to mammals, e.g. for the treatment or prevention of diseases responsive to the inhibition of thromboxane synthetase, comprising cardiovascular disorders such as thrombosis, atherosclerosis, coronary spasm, arrhythmias, cerebral ischaemic attacks, migraine and other vascular headaches, myocardial infarction, angina pectoris, hypertension; respiratory disorders, such as asthma and apnea; and inflammatory disorders. Inhibition of thromboxane synthetase also has been noted to decrease metastasis in certain classes of tumors, and the compounds of this invention may thus be useful for the treatment of certain carcinomas.